This makes for attention-grabbing headlines, but in fact the study had virtually nothing to do with food addiction. The study made no attempt to measure addictive behavior related to refined carbohydrate or any other food, nor did it aim to do so.

So what did the study actually find, why is it being extrapolated to food addiction, and is this a reasonable extrapolation? Answering these questions dredges up a number of interesting scientific points, some of which undermine popular notions of what determines eating behavior.

Before we dive in to the study, I want to take a moment to discuss food addiction. In common parlance, if we really like a food, we're motivated to get it, or we tend to eat more of it than we think we should, we often say we're "addicted" to it. This is not quite accurate, but it does point toward an important truth. Clinical food addiction is a serious phenomenon, akin to drug or gambling addiction, that only affects a few percent of the population. Food is something we have to consume to survive, which makes it qualitatively different from drugs of abuse, although of course we don't have to consume Slurpees.

Addiction is a pathological over-activation of the reward system in response to a specific stimulus (e.g. crack cocaine), resulting in an enhanced level of motivation to obtain that stimulus, to a point where the behavior is damaging to a person's life and/or health. Some have argued that obesity cannot be defined as a state of food addiction, though binge eating may qualify (1). I think that's a reasonable perspective.

The more important point is that you don't have to be clinically addicted to a food to overconsume it. Addiction is a pathological over-activation of the reward system, but there are many shades of gray between not caring about a food and being addicted to it. Ordering chocolate cake and ice cream after a large meal doesn't mean you're addicted to chocolate cake and ice cream, it just means it's highly rewarding. Your brain isn't broken; it's doing what it's supposed to do when it encounters a calorie-dense food rich in fat, sugar, and starch. So while most people may not be literally addicted to food, they do experience an enhanced motivation to eat certain foods that works via the same brain systems that mediate addiction.

The Study

The paper was published by Dr. David Ludwig's group in the American Journal of Clinical Nutrition (2). In a randomized crossover design, they gave 12 overweight or obese men a beverage that was either high glycemic index (HGI) or low glycemic index (LGI), meaning that the former caused a larger increase in blood glucose than the latter. Then, they measured blood glucose and hunger over a 5-hour period. At the 4-hour timepoint, they measured changes in brain blood flow (an indirect indicator of activity) in 25 different brain regions by fMRI.

As expected, people consuming the HGI beverage had a greater increase in blood glucose. At 5 hours, the HGI group was back to baseline blood glucose, while the LGI group was still modestly elevated, with a small difference between groups. Hunger ratings were higher in the HGI than LGI group. This is consistent with some studies showing that lower glycemic carbohydrate foods tend to be more satiating at a single meal. There are notable exceptions to this trend, such as potatoes, which are one of the most glycemic foods and also one of the most satiating (2B).

The key finding of the paper is that activity of the nucleus accumbens, a brain region central to reward processing and addiction, was higher in the HGI group than the LGI group at 4 hours, a timepoint at which there were differences in blood glucose levels and hunger between groups.

The authors suggest in the discussion that the drop in blood glucose in the HGI group after hitting peak glucose is responsible for the increased hunger, and activation of the NAc, which they interpret as an increase in the subjects' desire for food:

The decline in blood glucose (and other metabolic fuels) in the late postprandial period after a high-GI meal would not only constitute a powerful homeostatic hunger signal but also increase the hedonic value of food through striatal activation. This combination of physiologic events may foster food cravings with a special preference for high-GI carbohydrates, thereby propagating cycles of overeating

This interpretation goes far beyond the findings of the paper itself, and is based on a number of assumptions, which I'll examine below.

Discussion

One of the most pervasive ideas in the diet-health sphere, and to some extent even in the scientific literature, is that when you eat rapidly digesting carbohydrate, this causes an increase in blood glucose and insulin, followed by hypoglycemia (the "crash"). This low level of blood glucose then causes hunger and cravings. It's a simple, logical idea that has virtually no scientific support.

Hypoglycemia definitely causes hunger and food cravings (3). That isn't in question. The problem is that the level of hypoglycemia that causes hunger (below 51-65 mg/dL depending on the study; 3, 3B) is rare in non-diabetics, no matter what kind of carbohydrate they eat. For example, Dr. Ludwig's study reported that participants had an average fasting glucose of 88 mg/dL. This is a normal level of fasting glucose. At the lowest level of the HGI group's post-meal "crash", they had a blood glucose of 85 mg/dL-- a trivial 3 mg/dL below fasting, and nowhere near hypoglycemic. The LGI group had a blood glucose of 95 mg/dL, only 10 mg/dL higher than the HGI group. Could a difference in blood glucose this small account for the measured differences in hunger? Probably not, given that previous studies have struggled to find satiating effects of much higher levels of blood glucose in humans.

The unfortunate reality is that there is no compelling evidence that blood glucose fluctuations within the normal range cause differences in hunger and food intake. When you get into the abnormal range of true clinical hypoglycemia and hyperglycemia, then you see big effects, but fluctuations within the range of what are observed when non-diabetic people eat food have not been convincingly linked to hunger, craving, or food intake, despite quite a bit of work in the area. Here is a quote from a 2006 review paper on glucose-sensing neurons (4):

There is no question that severe [hypoglycemia] can stimulate feeding and that high concentrations of glucose placed in the brain can terminate feeding. However, it is uncertain whether any of these findings implicate glucose as a primary mediator of meal to meal intake under physiological conditions... In fact, no one has ever demonstrated that meal initiation or termination can be manipulated by altering brain glucose levels within the limits found during normal ingestion.

That doesn't necessarily mean this hypothesis is incorrect-- maybe future experiments will support it when we get better research tools-- but the hypothesis is often assumed to be correct in the media and even the scientific literature, despite a lack of clear evidence to support it. This is putting the cart before the horse.

There is another hypothesis out there, proposing that it's not the absolute level of glucose that matters, but rapid changes. Jenny Ruhl advocates for this idea in her book The Truth About Low Carb Diets. Again, this is a logical hypothesis, and I would love for it to be correct because it's so simple, but it has not received much convincing support from science at this point. To be fair, it's an exceedingly difficult question to answer properly, so it's possible that we just haven't found the right way to test the hypothesis yet. Ruhl bases her hypothesis on observations she and other people have collected using their home blood glucose meters.

It is true that there are glucose-sensing neurons, and that they can impact hunger and food intake in response to glucose levels under some circumstances (e.g., true hypoglycemia). These neurons often integrate a variety of signals of energy status (e.g. leptin, ghrelin, insulin, CCK, glucose, fatty acids) to determine hunger state, which is why they're sometimes called "metabolic sensing neurons" (4). Glucose probably plays some role in hunger, but it may simply be too small to detect under normal circumstances because it's one of many signals these neurons integrate. It's possible that the effect of glucose is heightened in certain metabolic contexts, but this remains to be tested. If I had to speculate based my own personal gut feeling, I'd say that blood glucose (or some variable related to cellular glucose availability) probably does play some role in hunger and food intake, and that this effect is probably heightened in certain individuals. However, that idea remains in the realm of logical speculation-- not fact.

This brings us to an additional point. We see what we can measure, and we tend to base explanations on what we see. The LGI and HGI meals caused a number of physiological effects, both measured and unmeasured. For example, if blood glucose remained elevated in the LGI group at the four hour timepoint, that means glucose was presumably still present in the gut and being transported from the gut into the bloodstream, even though that wasn't directly measured. Since we know that there are glucose receptors in the gut, and that these play a role in satiety, this presents a (in my opinion) more compelling explanation for the increased satiety they observed. Longer residence time of glucose in the small intestine = prolonged satiety.

Now let's discuss the fMRI finding. The nucleus accumbens (NAc) is intimately involved in reward processes, including food reward. They showed that at 4 hours, the HGI group had a higher activity of the NAc than the LGI group. This finding is interesting from an academic perspective, but it's difficult to interpret. Normally, when you want to measure reward system activation, you present some sort of stimulus to the subject. For example, as my colleague Dr. Ellen Schur does (5A), you present people images of tasty foods, average foods, and non-food items, and you see how brain activity differs between those conditions. Then you know that the brain responses were specifically to food cues. In contrast, in the current study, subjects were sitting in the fMRI machine getting scanned without any kind of stimulus.

So what does it mean for a person to be sitting in an fMRI machine and his NAc is lighting up spontaneously without any sort of cue? Does it mean the brain has received a reward and is processing it; does it mean the brain is seeking an additional reward; or something else entirely? Does it mean the subject wants to drive a fast car, eat a hamburger, or sleep with a beautiful woman? No one knows! The point is that we have no idea if this spontaneously increased NAc activity is causing an increased desire for food, favors addiction, etc.

If I had to offer an explanation for this result, I'd propose that prolonged small intestine exposure to glucose in the LGI group led to increased satiety, which led to decreased NAc activity relative to the HGI group. We know that the satiety system suppresses food reward perception, which is why we aren't as interested in food when we're full. This explanation is still speculative, but it rests on mechanisms that have been clearly supported by research in other contexts.

Practical Implications

Before moving on, I'll restate that this study has value in an academic sense-- it expands our understanding of the relationship between food intake, hunger, and brain activity. But the practical implications, as suggested by news articles and the study's discussion section, are murky.

First of all, most meals don't differ in glycemic index as much as these two did (2.3-fold difference). They were specifically designed to create a very large difference in glycemic index-- a difference that would be difficult to achieve in real life.

Second, as I've pointed out many times, the glycemic index is not a reliable indicator of the satiating effect of foods. The white potato has one of the highest glycemic indices of any food, yet it's also highly satiating per calorie (5). No one becomes addicted to plain potatoes, despite the high glycemic index, nor do people generally crave or overeat plain potatoes. Now, put some sour cream, bacon, chives, and salt on that potato, and there's something people will crave and overeat. Is that because of the glycemic index, which declined quite a bit after you put the toppings on? Or something else about that food?

The glycemic index also doesn't correspond very well with how refined a food is. For example, white bread and whole wheat bread have approximately the same glycemic index. White pasta and whole wheat pasta do too. So do white rice and brown rice. If you think there's a difference in the health impact of these refined vs. unrefined foods, glycemic index doesn't capture it.

The biggest problem with the glycemic index literature (in my opinion) is one that does not apply to this particular study, which was relatively well controlled. Many studies on the health impacts of the "glycemic index" compare diets that differ from one another in many ways. If you feed one group a diet consisting of beans, nuts and fruit, and another group a diet of white bread, pastries and soda, you can call the diets "low GI" and "high GI", but that doesn't mean the effects you observed were attributable to differences in blood glucose. There are so many other differences between the two diets that it's impossible to know what caused the effects you observed. Yet these types of studies are frequently used to support the hypothesis that differences in blood glucose influence satiety, body weight, and health.

Another big problem is that the glycemic index literature overall contains little support for the idea that low glycemic index eating styles have a significant long-term effect on body weight and metabolic health. If the authors' hypothesis is correct that high glycemic index foods "foster food cravings with a special preference for high-GI carbohydrates, thereby propagating cycles of overeating", then this should be observed in long-term controlled trials comparing LGI with HGI eating styles. However, most studies over 10 weeks long have shown little or no effect on these outcomes in non-diabetic individuals (6), with the three longest trials (4, 6, and 18 months) showing no real advantage of LGI eating on body weight or glucose metabolism (7, 8, 9). The large Diogenes study did find that LGI eating modestly slows weight regain following calorie restriction-induced weight loss, though the study wasn't really designed to isolate the glycemic index from other food properties like fiber content (10). At least this shows that the advice to reduce glycemic index has a measurable impact in certain contexts, even if the impact is small.

Despite the unimpressive performance in controlled trials, the glycemic index is enthusiastically presented as an effective way to prevent and treat obesity and metabolic dysfunction in non-diabetics. This is based largely on observational studies, which have sometimes found that HGI eating is associated with obesity and diabetes risk. While I don't totally dismiss the findings of these studies, I think they're hard to draw firm conclusions from, given their inherent limitations and the divergent results of controlled trials.

Conclusion

Although it adds meaningfully to the literature on food consumption, hunger, and brain activity, this study did not support the conclusion that "refined carbs are addictive", nor did it show that differences in blood glucose within the normal range cause hunger or food craving, nor that a high glycemic index per se contributes to obesity. Certain refined carbohydrate foods are indeed highly rewarding, and can lead to craving and overconsumption, but whether this relates specifically to their effects on blood glucose remains unclear. I look forward to research clearly supporting the idea that changes in blood glucose within the normal range have a significant impact on hunger, satiety, food craving, obesity, and addiction.

41 comments:

RE A satiety index of common foods:-I can't read the full study, but I can read the full study of An insulin index of foods: the insulin demand generated by 1000-kJ portions of common foods, which appears to use the same foods in the same amounts. Note:-"Potatoes Russet potatoes Peeled, boiled for 20 min, and stored at 4 °C overnight; reheated in a microwave oven for 2 min immediately before serving"Overnight refrigeration of cooked potatoes causes the formation of some resistant starch, which has a low GI. A mixture of high GI & low GI starches spreads the entry of glucose into the blood over a long period of time. This may explain why the potatoes in this study had high satiety.

In practice, people usually cook potatoes and eat them while they're still hot, which doesn't produce any resistant starch.

As a side note, when I started using insulin my occasional lows (below 50, and even a few below 40) did in fact cause a lot of hunger. At first, but no longer. I use dark chocolate pieces (4 grams of carbs) per formula to return to goal BGs. I am seldom tempted to have more than the formula determined dose, despite liking chocolate a lot.

"The problem is that the level of hypoglycemia that causes hunger (below 51-65 mg/dL depending on the study; 3, 3B) is rare in non-diabetics..."

You've said this before. I personally experience these symptoms after eating carbs, reliably, and consistently. I consider that to be a more important "fact" than whether or not one can dig up a study explaining the phenomena in the literature; which is not the final arbiter of those things we regard as facts. (I'd wager you'll find few studies finding that hitting yourself in the head with a hammer is inadvisable, yet that is also a fact...)

Nevertheless, you're technically correct: since low-blood sugar is a required component of a hypoglycemia, I most likely don't have hypoglycemia. Instead, I probably have what's known as "idiopathic postprandial syndrome":

http://www.ncbi.nlm.nih.gov/pubmed/7227659

Which is similar to hypoglycemia in its effects, but is missing the key ingredient of low blood glucose. It does have real, testable physiological manifestations, however:

"The use of the plasma epinephrine response in the diagnosis of idiopathic postprandial syndrome."http://www.ncbi.nlm.nih.gov/pubmed/6690833

The unpleasantness of which are one of the main reasons I enjoy a low-carb diet.

This is apparently quite common, and hunger is one of the symptoms, although the mechanism is unclear; and there seems to be no research being done on the condition.

But it would help to demonstrate that folks such as myself who feel hunger a few hours after a glucose bolus have some support in the literature.

Also, I feel like there may be some sort of negative effect of highly refined foods that goes beyond the "crash" that many people probably feel. I used to be 30 pounds heavier and felt addicted to certain foods (ice cream, peanut butter sandwiches with honey, oreos). I'd feel sick if I abstained from these foods for a few hours. Eat them. Feel sick in a few hours. Eat more...it was a nasty cycle.

Eating baked white potatoes with butter and cheese does not illicit such a nasty feeling so I wonder if something(s) beyond macronutrient composition /GI or G. load are at work -- food additives???

" At the lowest level of the HGI group's post-meal "crash", they had a blood glucose of 85 mg/dL-- a trivial 3 mg/dL below fasting, and nowhere near hypoglycemic. The LGI group had a blood glucose of 95 mg/dL, only 10 mg/dL higher than the HGI group. Could a difference in blood glucose this small account for measured differences in hunger?"

But the group which consumed HGI food had a larger increase in a blood glucose , so it is reasonable to say that their level of blood glucose basically crashed, while in LGI group the change in BS was more gradual. It looks like the speed of the change is the major difference producing the difference in hunger levels.

In the satiety and insulin index study, the potatoes they used produced a large rise in blood glucose-- larger than any other food tested. I don't know whether there was resistant starch present or not, but it didn't prevent a large glucose and insulin excursion in any case.

Hi Tucker,

I don't doubt that what you say is true-- my main point is that we can't assume that phenomenon is due to changes in blood glucose, when many other things are happening in the body simultaneously. A second point is that your experience may not apply to the "average person", as suggested by the clinical trials.

Hi Robert,

Hypocretin/orexin neurons are activated by elevated glucose, and Dan Pardi has argued convincingly that this COULD be a reason for post-meal sleepiness, which some feel is higher with high carb food. I don't know about the role of melatonin.

I'm not saying that I know for sure that changes in blood glucose aren't involved in what you experienced, what I'm saying is that research up to this point hasn't clearly supported that hypothesis and we can't just assume it's correct.

I also can't tell you for sure what accounted for your cycles of overeating, but I'm skeptical that it's blood sugar swings, given that some of the foods you mentioned (e.g. ice cream) are not especially glycemic (brown rice and whole wheat bread are higher). If it was really all about glucose, why not just eat plain bread and potatoes? Personally I think a more compelling possibility is that you were driven by the reward value of those foods independently (or partially independently) of blood glucose changes, and you were addicted to them or close to it. Rats will literally go through full-blown withdrawal symptoms that resemble morphine withdrawal when you give them access to a sweetened beverage for weeks and then take it away. It presumably has nothing to do with blood glucose because their regular chow is ~65% carbohydrate. I don't know all the details of your situation so take it with a grain of salt, but those are my thoughts.

The first thing I notice is that the study involved "12 overweight or obese men", it does not say that they were necessarily insulin resistant. Perhaps that is covered in the original study, but I don't think it's safe to assume that every person who is overweight by BMI standards or even obese is necessarily insulin resistant.

Secondly, it may be true that generally people (insulin resistant or not) don't become hypoglycemic after a significant serving of high glycemic index foods, but for those of us who experience the "crash and burn" (which is not fatigue as one commenter implies, but shakiness, anxiety, sweating, weakness, headache, feeling faint, and a hunger that is only satisfied by MORE high GI foods), Jenny Ruhl posits that we may be experiencing "false hypos": http://diabetesupdate.blogspot.com/2007/07/type-2s-understanding-false-hypos.html

It may be that the degree of excursion in blood glucose levels (even if they remain above hypoglycemic range) and the degree of insulin response triggers this physiological response, even when the blood glucose levels are NOT truly hypoglycemic.

Personally I have experienced this--all the symptoms of hypoglycemia, and then was shocked to find my blood sugar in the mid to low 80's. (I have severe PCOS-related insulin resistance) This was a constant and almost daily occurrence when eating a SAD diet. By reducing my carbs and eating adequate fat and protein with the carbs, my blood sugar is much more steady and I rarely experience this feeling, even with much lower blood glucose levels. And I'm not constantly hungry and looking for my next snack or meal. I can easily go 9 or 10 hours during the day without eating, something that was impossible for more than 2 or 3 hours when I ate high glycemic foods.

It may be that this constant need to eat every two or so hours is not necessarily a true "addiction", and it may not be true hypoglycemia, but it is a REAL physiological response to something that the high glycemic foods trigger.

Stephen - I value your "contrarian" outlook on things compared to the lowcarb blogosphere. I present to a lot of young people about carbs, fats, insulin etc, and the strongest feedback I get from audiences is how they dislike being unable to concentrate before lunch, and feeling tired afterwards.

Many of the people I present to subsequently drop a lot of sugars and carbs and again the strongest feedback I get is how much they like no longer being dependent on the '3 hour feeding cycle'.

Much as I appreciate your remarks on the role of carbohydrate and insulin being unproven in 'postprandial somnolence', there is vast anecdotal evidence of it being resolved by dropping the carbs.

So something is going on there, even if the mechanisms haven't been clarified yet.

Interesting study. Yes I remember all the media attention. So glad you dissected it out for us this carefully.

I have just one anecdote to add. If I don't consume some fat with a meal, I will be hungry again within 1-2 hours post-prandial. Thus I am not satiated by eating fibre, protein or carbohydrates contained in a low fat meal. I have read that fat is intrinsically more satiating than protein or carbohydrates and perhaps it's due to slowing down of peristalsis and glucose absorption. Any thoughts on why I seem to need fat in my meals? I'm vegan, so the fat I consume is typically nut or seed butters.

The biggest hunger spike seems to occur right after dinner, which lately has contained very little, if any, fat. I am not eating high-glycemic index food by any stretch of the imagination, avoiding grain and fruit in particular. And I don't crave particular foods so I don't think it's food reward.

I just don't know how anyone can persist with an ultra low-fat diet. There must be genetic or metabolic differences in such individuals.

I don't have access to the full paper and I want to understand the context of the term "satiating." Did they find that the test subjects were full from eating potatoes and refused any kind of food or did they eat potatoes until they couldn't eat another potato? In other words, was it:

Yes that was my direct experience when initially going "low carb". After reverting to a more normal, somewhat higher carb diet, I also found out that by simply spacing meals six hours apart, and doing this consistently day-after-day, one lost any appetite around lunch time and could eat again at 3 p.m. without hunger. That was how I broke the 3-4 hour feeding cycle. If you eat consistently meals that are 3-4 hours apart, regardless of their carb content, your body becomes habituated to such a frequent feeding cycle. I think that is why snacking between meals is such a bad idea - it opens the door to hunger. At least in me. Making a six-hour gap between breakfast and lunch has been a lifesaver for me.

Hi How does food reward relate to fat accumulation? Yes, the food stimulates storage hormones and gets stored, but this should provoke anorexigenesis. E.g. if I eat 200g of cadburys chocolate I will be warm, fidgety, energetic and not hungry. Most lean individuals will relate to this.This is what keeps weight stable.

Feeding powerfully modulates the circadian rhythm. If one eats a large meal of protein and fats, cholecystokinin is released which promotes the onset of sleep through inhibition of orexin neurons and modulation of clock genes.

I think it would be of value if you spoke of the circadian rhythm in relation to food.

Also, I think sucrose does have significant opioidergic properties as it tends to temporarily relieve my depressive disorder. I do not think it is neccesarily obesogenic for all people though. High sucrose diets are not conducive to good health.

@bert hubertI'm not sure I'd describe Guyenet as contrarian. A contrarian is generally someone who opposes the established authority, but as a nutrition academic who generally agrees with the consensus view he is the established authority on this topic.

As for low-carb it might be that higher carb foods tend to be more satiating, palatable, and easier to overeat (ie people understand a hunk of butter is fattening in a way bread isn't, so they overeat the bread more readily). I know going low-carb with a jar of peanut butter didn't reduce my cravings, but a bunch of raw broccoli sitting on my desk sure did.

Thanks for the hypocretin/orexin neuron and food reward info, Dr. G. I'll have to read more about them.

Also, thanks for taking on shibboleths within nutrition. It is tough to buy-in to a lifestyle based on a hypothesis and then realize the hypothesis underpinning your lifestyle may be incorrect (see vegans).

This would explain the blow-back you get from low-carb folk and why vegans try to destroy me on Huff Post when I point out that the healthy user effect (and socio-economics) are generally at work in obs. studies looking at Western vegetarians.

Anecdotally, I only lost the last 10 lbs of college chub after stopping low-carb and eating potatoes/rice. Go figure.

Well said. I think plain baked potatoes present a very strong case against the idea that blood glucose changes or insulin per se cause us to overeat.

My own experience is that I have problems with overeating just like anyone else, but that the only requirement is the food must be hyper-palatable to me. Seems like refined carbs per se aren't palatable to me, but carbs + fat is, despite its lowered glycemic index. Don't know why so many people can't accept that its anything but the carbs.

Low carb diets work for me as well. I don't feel the ups and downs that others feel, I just feel like eating all day long when I'm eating palatable junk. What I do theorize is that even with low carb, after a while my brain re-values the foods I'm allowed to eat and I start choosing the most fattening of the low carb foods so the effect wears off and some weight regain occurs.

Do you know if your AHS talk is available anywhere on the internet yet?

Actually, the Dr. Ludwig's study is not about LC versus low-glycemic-index diet, the discussion is about a difference between eating refine carbs and not-refined ones, and the observation was made on obese guys, however metabolically healthy jugging by their FBS, not on naturally thin individuals who just feel warm/move more after eating junk foods, which is a progress.

LCarbers most of the time are self-selected group of people who failed on a low-glycemic diet, so they see little difference in the effect of refine carbs and unrefined ones.

The term 'idiopathic postprandial syndrome' seems more apt in accounting for the range of symptoms accompanying 'low'/fluctuating post-prandial BG levels.

The term does a better job as it accounts for:1. individual variability regarding what can be called 'low' BG and a return to 'normal' BG levels2. and doesn't automatically consider the postprandial BG fluctuations 'irrelevant' simply because the BG levels don't follow criteria that may very well be outdated

Hypoglycemia will cause serious damage if it isn't dealt with quickly as it is an acute presentation of an energy management issue...SO

Couldn't the chronic BG fluctuations presenting in people with a wide variety of mood and adrenergic symptoms be a LIKELY CANDIDATE to explain the problem? (even if the hypoglycemic threshold isn’t reached)

After all, hypoglycemia is a state of emergency - surely brushing close to it multiple times a day cannot be great...

Galina, the study compared two equally refined carbs: corn starch and corn syrup. Some people use the term refined not for carbs which have had the germ/bran/micronutrients removed, but for those which are processed in such a way as to raise the glycemic index. To me this makes no sense, because it means whole wheat flour is 'refined' because its GI is higher than wheat berries, and corn starch is UNrefined because its GI is lower than corn syrup.

LCarbers are mostly people who failed on a low-glycemic diet, are they? That's interesting. To me that suggests their pancreatic beta cells are not working properly. If they're not sensitive enough to glucose, any carb foods can cause blood sugar swings due to delayed insulin release and overshoot. I just found a study showing that low beta cell glucose sensitivity correlates with BMI and waist circumference even in people with normal glucose tolerance.http://www.ncbi.nlm.nih.gov/pubmed/20805281

Jane, probably, it will be more accurate for me to say that LCarbers are the people who don't tolerate carbohydrates well, and for that reason limit the amount of it regardless of GI .So, from the LCarber's perspective, the study about obese man eating either refined or un-refined carbohydrates is not particularly relevant, however it is refreshing to see research to be done on not thin healthy people.I am not ready to discuss GIs of different products , but it looks like the people in the study reacted differently on LGI foods than on HGI ones.

I have no problem with the term "idiopathic postprandial syndrome". This is a term that replaced "postprandial hypoglycemia" after the discovery that these hypoglycemia-like symptoms don't usually correlate with actual hypoglycemia. Idiopathic means we don't know what causes it, i.e. there is no assumption of hypoglycemia. It just describes a cluster of symptoms that some people get after they eat.

Could IPS relate to some aspect of glucose metabolism? I think it's entirely plausible, perhaps even likely, but the critical factor isn't necessarily blood glucose. Remember that hypoglycemic symptoms result from alterations in intracellular neuronal glucose metabolism that are an indirect result of extracellular glucose. There are other ways to alter intracellular neuronal glucose metabolism (e.g. 2-deoxy glucose) that don't involve changes in plasma glucose.

This is an area that needs more work. My only point in this post is that we shouldn't jump to conclusions about mechanisms.

Stephan, a quick question: are there any blog posts on your site related to the topic of fat intake and satiety? Also, are there scientific data to support the notion that dietary fat is more intrinsically satiating than other macronutrients? It seems to be a common theme in the 'low carb' and 'paleo' communities, and I have noticed it with myself. Are there differences in satiety between saturated and unsaturated fat?

Why is cholecystokinin (CCK) not discussed? This hormone acts as a hunger suppressant and is released when fat is consumed. This is well documented in the medical literature.

I suspect this must have played some role in the study. I also think it's why many commenters have report anecdotal evidence that they feel less hungry once they drop carbs for fat. It makes scientific sense.

There is no scientific evidence to support the idea that fat is more satiating than other macronutrients-- in fact, the evidence fairly consistently shows it to be less satiating than protein and carbohydrate per calorie. This is because of its calorie density and palatability, because when these are controlled, it is equally satiating as carbohydrate (though less than protein). I think people get confused because fat often comes with protein (e.g. meat), which is highly satiating. But the fat itself is not particularly satiating, per calorie consumed.

Hi Mark,

CCK is one of many satiety signals. Some satiety signals respond more to fat (e.g. CCK), others respond more to carbohydrate (e.g. amylin). Knowing what CCK is doing, or what any individual satiety signal is doing, is not sufficient to predict satiety perception. The system is too complex.

There's a new satiety hormone called uroguanylin which could be the most interesting of them all. It works by activating an enzyme that needs metal cofactors, meaning it could signal satiety differently for refined and unrefined carbs. The metals are magnesium and manganese, which are high in unrefined carbs and low or absent in refined ones. I think Ludwig can be criticised for muddying the waters about the difference between refined and unrefined carbs. To my mind glycemic index is a red herring.

BTW Stephan, you said twice that nucleus accumbens activity was higher in the LGI group than the HGI group. You meant lower, I imagine.

Why is glycemic index a red herring? Clinically it seems to be useful as there is evidence that low GI diets do promote weight loss. Can you be more explicit in what you mean? Do you mean that it doesn't adjust for total glycemic load?

Many things happen when you ingest glucose. It is detected by receptors in the mouth and small intestine, and this results in hormone release and nerve signals that coordinate the body's response to it. It is absorbed and transported through the blood. The brain senses glucose ingestion indirectly (by glucose receptors in the mouth and gut) and directly (by an increase of blood glucose). It is metabolized by tissues.

Any step in this process could be involved. We focus on circulating glucose because it's easy to measure and it has been linked to similar symptoms in the context of actual hypoglycemia.

The brain is what initiates hypoglycemia, and probably IPS since it resembles hypos symptomatically. Normally, neurons detect low circulating glucose through the action of the glucose-sensitive enzyme glucokinase and coordinate the counterregulatory response to hypoglycemia (glucagon and adrenaline release, hunger, etc). This happens due to changes in neuronal glucose metabolism that are triggered by low glucose availability in the brain, but since this response sometimes occurs in the absence of actual low blood glucose it could involve influences on neuronal glucose metabolism that are independent or semi-independent of circulating glucose.

You can cause a counterregulatory response to hypoglycemia without lowering blood glucose if you interfere with brain glucose metabolism, e.g. with 2-DG and other non-metabolizable glucose analogs. It's possible changes in brain glucose metabolism could be related to IPS, but that's just an educated guess.

Here's what I'm thinking. The evidence seems to indicate that glycemic index doesn't matter unless your glucose regulatory system is not working properly. If it is working properly, blood sugar will be stable because insulin is produced in the right amount at the right time, and glucose enters tissues at the right rate and gets released by the liver exactly when it's needed. What you don't want is blood sugar swings, and a lot of people do seem to have them although as Stephan says the link with symptoms is fuzzy. These people might benefit in the short term from avoiding high GI foods, but in the long term what they need to do is heal their glucose regulatory system.

The evidence suggests that this system malfunctions mainly because of iron overload and deficiencies of magnesium and manganese. Other deficiencies too of course, but these seem to be the most important. You can't make ATP without magnesium, and you can't prevent iron-dependent damage to your mitochondria without manganese. But unrefined carbs, which are arguably the best sources of Mg and Mn, have a high glycemic index just like refined carbs do.

I recently had a lengthy argument with a Taubes disciple (carbs make you fat). Largely using evidence from here I was eventually able to argue them down to a somewhat narrower hypothesis of something like "refined fructose and sugar make you insulin resistant and if you're insulin resistant carbs will make you fat". I think he's still really overestimating the role of fructose and sugar as being a source of calories in causing insulin resistance but I was curious if there was any basis to high GI food causing extra weight gain for insulin resistant people.

As you mentioned high GI foods can do other bad things if you're insulin resistant but is weight gain among them?

Regarding reactive hypoglycemia, I just wanted to mention to any of those afflicted that I suffered from this, or from whatever it's called now, for about 15 years. It wasn't until I started supplementing with (what I suppose are pharmacological doses of) biotin that it completely resolved. 500mcg twice a day was enough to allow me to eat anything without issue. I'm guessing that the underlying problem lies with poor activity of the biotinidase enzyme. Whatever the cause, I was thrilled to have found a solution.

Interestingly, the biotin also resolved an issue with overly dry skin that I had for the same period, presumably as a result of facilitating proper fatty acid metabolism and sebum secretion.

Hi aluchkoI'd have to say, yes and no. Refined sugars make you insulin resistant in at at least two ways. First of all, they make the pancreas produce insulin without providing the micronutrients it needs to repair itself, which it should be doing all the time. If it does not produce insulin in the correct oscillatory pattern, insulin target tissues cannot respond to it properly. And in any case, they need the micronutrients themselves.

Second, fructose is a particular problem because it interferes with metal metabolism. Fructose-fed rats get copper deficiency due to down-regulation of the gut copper transporter (I have no idea why fructose does this). In humans, even a small dose of fructose can cause 'oxidative stress' probably by removing iron from hemoglobin. Free iron is very toxic. http://www.ncbi.nlm.nih.gov/pubmed/19763999

Your question was, can high GI foods make you fat if you're insulin resistant? Well micronutrient deficiencies are expected to make adipose tissue malfunction so it doesn't burn much fat and stores it instead. So high GI refined carbs might do it, but high GI unrefined carbs might not.

Plain sugar water can elicit addiction-like effects in rats, but there is no evidence that this is due to its ability to increase blood glucose.

Also I'm not convinced most humans would be drawn to plain sugar water with no flavorings or carbonation-- it's just not that palatable. I'm pretty sure plain sugar water has a low addiction potential in humans. Soda has a higher addiction potential, but it also contains flavorings, carbonation, and often a habit-forming drug (caffeine).

In my experience, one can become addicted to almost anything. I have a colleague who drinks about 2 L of diet cola beverages per day. It is clearly not the sugar but perhaps the combination of carbonation, caffeine and vanilla flavoring. However, it is probably true that very few humans would ever become addicted to plain sugar-water. Good luck with your talk in Portugal. I am certain it will be well-received and I wish I could attend.

About Me

I'm a writer and science consultant with a background in neuroscience and obesity research. I have a BS in biochemistry and a PhD in neurobiology. I'm the author of "The Hungry Brain: Outsmarting the Instincts That Make Us Overeat".

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